Cationic amino acid transporter-2 mRNA induction by tumor necrosis factor-alpha in vascular endothelial cells.
Nitric oxide (NO) synthesis may be coupled to the activity of the cellular L-arginine transporter, namely the cationic amino acid transporter. The present study examined tumor necrosis factor (TNF)-alpha-induced alterations in the gene expression of the cationic amino acid transporter (CAT) and NO production in human umbilical vein endothelial cells. In quiescent endothelial cells, CAT-1 mRNA expression, determined by reverse transcription-polymerase chain reaction, was dominant to that of CAT-2. TNF-alpha (10 ng/ml for 1-24 h) induced a time-dependent increase in CAT-2 but not CAT-1 expression. Moreover, TNF-alpha (1-30 ng/ml) treatment for 6 h induced a concentration-dependent increase in CAT-2 mRNA expression. The upregulation of CAT-2 expression by TNF-alpha was associated with enhanced nitrite accumulation in the culture medium (70% increase compared with vehicle-treated cells at 24 h). Thus, induction of the cationic amino acid transporter may constitute one mechanism for the TNF-alpha-induced NO production in human umbilical vein endothelial cells.
Irie
K
K
Department of Pharmacology, Tokyo Women's Medical College, Japan. kirie@research.twmc.ac.jp
Tsukahara
F
F
Fujii
E
E
Uchida
Y
Y
Yoshioka
T
T
He
W R
WR
Shitashige
M
M
Murota
S
S
Muraki
T
T
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha